By studying the spectral properties of the underlying operator corresponding to the M/G/1 queueing model with optional second service we obtain that the time-dependent solution of the model strongly converges to its s...By studying the spectral properties of the underlying operator corresponding to the M/G/1 queueing model with optional second service we obtain that the time-dependent solution of the model strongly converges to its steady-state solution. We also show that the time-dependent queueing size at the departure point converges to the corresponding steady-state queueing size at the departure point.展开更多
Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is ...Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.展开更多
为了建立并分析牡蛎致敏大鼠模型,利用牡蛎过敏原Cra g 1,通过灌胃和腹腔注射相结合的方式致敏雌性棕色挪威大鼠(BN大鼠)。观察各组BN大鼠过敏反应及体重、体温、脏器指数、血象指标变化;通过ELISA法检测抗体、组胺变化;通过苏木精-伊红...为了建立并分析牡蛎致敏大鼠模型,利用牡蛎过敏原Cra g 1,通过灌胃和腹腔注射相结合的方式致敏雌性棕色挪威大鼠(BN大鼠)。观察各组BN大鼠过敏反应及体重、体温、脏器指数、血象指标变化;通过ELISA法检测抗体、组胺变化;通过苏木精-伊红(HE)及甲苯胺蓝染色观察组织器官变化。结果显示,实验组动物均发生过敏反应,对照组无明显症状;实验组动物体重显著低于对照组,脏器指数显著高于对照组,血液中细胞数量发生变化;另外,致敏期间实验组抗体及组胺水平均高于对照组;染色结果表明实验组大鼠脏器出现明显的病变损伤,肠道肥大细胞脱颗粒现象严重。该研究获得了Cra g 1蛋白致敏血清,同时证明BN大鼠是良好的动物致敏模型,为研究食物过敏原致敏机制及其体内免疫调节提供较好的依据。展开更多
基金supported by the National Natural Science Foundation of China(11371303)Natural Science Foundation of Xinjiang(2012211A023)Science Foundation of Xinjiang University(XY110101)
文摘By studying the spectral properties of the underlying operator corresponding to the M/G/1 queueing model with optional second service we obtain that the time-dependent solution of the model strongly converges to its steady-state solution. We also show that the time-dependent queueing size at the departure point converges to the corresponding steady-state queueing size at the departure point.
基金supported by NIH Grants R01NS092651 and R21NS111275-01the Department of Veterans Affairs,BX001148 and BX005899(to PHK)。
文摘Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.
文摘为了建立并分析牡蛎致敏大鼠模型,利用牡蛎过敏原Cra g 1,通过灌胃和腹腔注射相结合的方式致敏雌性棕色挪威大鼠(BN大鼠)。观察各组BN大鼠过敏反应及体重、体温、脏器指数、血象指标变化;通过ELISA法检测抗体、组胺变化;通过苏木精-伊红(HE)及甲苯胺蓝染色观察组织器官变化。结果显示,实验组动物均发生过敏反应,对照组无明显症状;实验组动物体重显著低于对照组,脏器指数显著高于对照组,血液中细胞数量发生变化;另外,致敏期间实验组抗体及组胺水平均高于对照组;染色结果表明实验组大鼠脏器出现明显的病变损伤,肠道肥大细胞脱颗粒现象严重。该研究获得了Cra g 1蛋白致敏血清,同时证明BN大鼠是良好的动物致敏模型,为研究食物过敏原致敏机制及其体内免疫调节提供较好的依据。
